With the advancement of the coronary intervention (Percutaneous coronary intervention; PCI) technique including a drug eluting stent (DES), post-PCI restenosis, which has conventionally been an issue of concern, has decreased. However, DES currently used in the world contains an immunosuppressant (e.g., sirolimus) or an anticancer agent (e.g., paclitaxel) and, as compared to conventional bare metal stents (BMS), DES has been reported to show, though it can suppress restenosis, higher incidence of acute coronary syndrome (ACS) in long-term prognosis, which is a fatal pathology, than BMS, and also clarified to not improve vital prognosis.
The presumed reason therefor is that, although acute coronary syndrome is mostly caused by rupture of arteriosclerotic plaque (plaque rupture), which is a comparatively mild to moderate lesion, rather than a severe stenotic lesion, which is conventionally the target of PCI, DES using an immunosuppressant or anticancer agent suppresses restenosis by suppressing neointimal thickening via prevention of smooth muscle cell growth, and its non-specific cell proliferation suppressive action prevents vascular endothelial regeneration and forms unstable plaque that becomes thrombus, thus increasing the incidence of ACS.
For improvement of vital prognosis, therefore, prevention of plaque rupture that causes acute coronary syndrome is important, and the development of a stent having a neointimal thickening suppressive action as well as a plaque stabilizing action by not preventing vascular endothelial regeneration and the like is considered to be an effective therapeutic strategy.
Peroxisome proliferator-activated receptor (PPAR) is a nuclear receptor which is activated by a ligand and functions as a transcription factor. PPAR has subtypes of α, γ and β/δ, and is deeply involved in the metabolism of carbohydrate, lipid and the like, and cell differentiation. PPARγ is known to be expressed on vascular endothelial cell, vascular smooth muscle cell, macrophage and T lymphocyte in arteriosclerotic lesion.
In arteriosclerosis, PPARγ agonists are considered to afford an anti-arteriosclerotic action by direct actions such as                protection and improvement of endothelial function by, for example, suppression of expression of adhesion factors such as ICAM-1, VCAM-1 and the like in endothelial cells, and the like        suppression of migration and growth of smooth muscle cells and MMP (matrix metalloproteinase) production in smooth muscle cells        suppression of monocyte differentiation and inflammatory cytokine production        promotion of reverse cholesterol transport mediated by ABCA1 in macrophages and the like.        
Pioglitazone, which is an insulin sensitizer, has a PPARγ agonist action and an apoptosis suppressive action, and is known to be useful for the treatment of atherosclerotic diseases, the prophylaxis or treatment of vascular reocclusion and restenosis after bypass operation and the prophylaxis or treatment of vascular thickening after intervention (percutaneous transluminal coronary angioplasty, percutaneous coronary revascularization, stenting, coronary endoscopy, intravascular sonication, percutaneous transluminal coronary thrombolytic therapy etc.) (WO99/25346, WO02/087580 etc.).
As a drug delivery system, moreover, nanoparticles encapsulating a nucleic acid compound (JP-A-2007-119396) and a drug eluting stent coated with nanoparticles encapsulating a physiologically active substance (JP-A-2007-215620) are known.